Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgery leads to significant modulation of the immune system, in which cytokines play a major role. Circulating interleukin 6 (IL-6) and IL-1 have been reported following surgery whereas tumor necrosis factor alpha (TNF-alpha) is only found in gut ischemia-associated surgery. We have investigated the consequences of surgery on in-vitro cytokine production by human monocytes stimulated by lipopolysaccharide (LPS) and staphylococcal toxic shock syndrome toxin-1 (TSST-1). Comparisons were made between the responsiveness of cells obtained the day before (D-1), during (D0) and after (D1, D2, D3) surgery. Patients undergoing abdominal aortic surgery (N = 9), carotid surgery (N = 4) and spinal surgery (N = 4) have been studied. A significant decrease of TNF-alpha, IL-1 beta and IL-1 alpha production by monocytes prepared from blood samples taken during the surgery was noticed, whereas IL-6 production was not significantly modified. On D2 a significant increase of monocyte responsiveness was observed and levels of cytokine productions rose back to initial values by the end of the follow up. The diminished in-vitro cytokine production observed during surgery might be the consequence of the effects of anaesthetic drugs, whereas the enhancement observed on D2 might reflect the surgical stress, leading to in-vivo priming of circulating monocytes.
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PMID:Influence of surgery on in-vitro cytokine production by human monocytes. 129 41

The role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN.
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PMID:Mild renal ischemia activates primed neutrophils to cause acute renal failure. 140 39

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
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PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order. As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day. Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid. A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor. Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage. By this sequence the final central mediator of shock and sepsis becomes systematically abundant. The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock.
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PMID:Reactive oxygen species, antiproteases, and cytokines in sepsis. 179 93

Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.
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PMID:Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor. 189 58

The enzyme xanthine oxidase participates in the pathogenesis of tissue ischemia-reperfusion injury by depleting purine pools and generating toxic oxygen metabolites. The role of xanthine oxidase in inflammatory cell populations has not been defined. We examined the level of xanthine oxidase activity expressed by murine leukocytes both in the resting state, and after in vivo and in vitro exposure to inflammatory stimuli. The contribution of xanthine oxidase to inflammation may vary among tissue compartments, so leukocytes harvested from several tissues were studied. Resident murine peritoneal macrophages consistently expressed xanthine oxidase activity (291 +/- 55 microIU/10(6) cells). Thioglycolate-elicited peritoneal macrophages contained similar levels of xanthine oxidase activity (265 +/- 42 microIU/10(6) cells). By contrast, resident murine alveolar macrophages expressed one tenth the xanthine oxidase activity (24 +/- 4 microIU/10(6) cells). Xanthine oxidase activity was also consistently found in murine peritoneal neutrophils (127 +/- 28 microIU/10(6) cells) but not in splenic lymphocytes. In vitro studies were performed to determine whether xanthine oxidase activity of resident peritoneal macrophages could be modulated by exogenous stimuli relevant to the pathogenesis of inflammation. Lipopolysaccharide caused a 62% +/- 9% reduction in cellular xanthine oxidase activity (p less than 0.02). Interferon-gamma alone had no effect on xanthine oxidase activity; however, interferon-gamma and lipopolysaccharide together caused a striking reduction in cellular xanthine oxidase activity, reaching 25% +/- 2% of unstimulated control cells (p less than 0.001). We conclude that murine macrophages and neutrophils are potentially important sources of xanthine oxidase activity in inflamed tissues. In addition, the activity of xanthine oxidase in macrophages is tissue specific and is modulated in vitro by proinflammatory stimuli.
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PMID:Expression of xanthine oxidase activity by murine leukocytes. 211 59

Prostaglandins and leukotrienes are ubiquitous mediators of a wide variety of physiologic and immunologic effects in liver function and disease. Although the biochemical, synthetic and catabolic pathways of these compounds from arachidonic acid are well known, their cellular mechanisms of action are less well understood. Numerous studies have demonstrated the role for leukotrienes in the pathogenesis and the protective action of PG in experimental animal models of liver injury. These have included models of liver cell damage due to ischemia, galactosamine, carbon tetrachloride, and lipopolysaccharide. More importantly, the results of these studies have led to the demonstration of protective properties of 16, 16 dimethyl PGE2 (dm PGE2) in a mouse model of viral hepatitis. These results have led to the use of IV PGE1 in the treatment of patients with fulminant viral hepatitis, where 71% overall survival was observed as well as in the setting of primary non function and recurrent hepatitis B following liver transplantation. While the mechanisms of prostaglandin hepatic protection are not well understood, it has been demonstrated that dm PGE2 abrogates the induction of tumour necrosis factor, leukotriene B4 (LTB4) and procoagulant activity by macrophages as well as attenuating the expression of major histocompatibility class antigens on the surface of hepatocytes, and may inhibit viral replication. Finally, prostaglandins are known to play a role in the renal dysfunction associated with cirrhosis and fulminant hepatic failure, and therefore further studies of these agents in the pathophysiology and treatment of liver diseases and their complications are warranted.
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PMID:Eicosanoids and the liver. 213 47

Escape of endotoxin from the intraintestinal site was investigated in experimental models of intestinal ischemia and during intraabdominal infection in rats. Following the instillation of Salmonella abortus equi endotoxin (S-form) into the proximal large bowel, we recorded the presence of the lipopolysaccharide molecule in the bowel wall, the intestinal lymph nodes, the peritoneal cavity, and in the liver sinusoids by immunohistochemical methods. At 3, 6, 12, 24, and 48 hr after the operative procedure, peritoneal fluid, blood, and tissue samples were taken. Survival rates were similar between the two test-groups (occlusion of the superior mesenteric artery [SMA] and cecal ligation and puncture [CLP]) and were not influenced by the amount of the injected endotoxin. There was no detectable morbidity in the sham-operated control animals with endotoxin doses up to 20 mg. Endotoxin could only be detected at 24 and 48 hr in the SMA group in the liver as well as in the peritoneal sediment and in intestinal lymph nodes. CLP and control samples remained negative throughout the observation period. Bacteria were found intraperitoneally within 12 to 24 hr in the SMA group and within 3 to 12 hr in the CLP group.
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PMID:The role of intestinal endotoxin in experimental peritonitis. 291 75

Endotoxemia is a frequent complication of many health disorders. It is characterized by systemic release of a variety of endogenous inflammatory mediators which effect cardiovascular depression, reductions in organ blood flow, tissue ischemia and derangements in cellular metabolism leading to death. During a continuous intravenous infusion of Escherichia coli lipopolysaccharide, the chronology of alterations in hepatosplanchnic blood flow, hepatic carbohydrate metabolism and pancreatic insulin secretion has been studied in awake Yucatan miniature pigs (Sus scrofa). Endotoxic shock in this model is characterized by reductions in portal venous and hepatic arterial blood flow, early transient increases in pancreatic insulin secretion, increases in the 3H-glucose-derived rates of glucose appearance and disappearance, profound hypoglycemia, hyperlactatemia and metabolic acidosis. Reductions in hepatic oxygen delivery are compensated for by enhanced oxygen extraction efficiency, but hepatic gluconeogenesis continues at an inadequate rate to compensate for increased glucose utilization. Experimental therapies including lidocaine, naloxone, captopril, dichloroacetate and glucagon each effect specific improvements in cardiovascular or metabolic function, but none significantly alter the composite derangements responsible for lethality in this model.
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PMID:Endotoxemia in Yucatan miniature pigs: metabolic derangements and experimental therapies. 353 41

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.
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PMID:Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats. 375 30


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